Chemical arrays find a variety of applications for the development of new physiologically active compounds, in diagnostics, as well as in other applications. The arrays provide a large number of different compounds in a relatively small space. For a proper array, each compound must have a uniquely defined area, which does not impinge on other areas and allows for detection of an event of interest. To provide arrays which can be used successfully, there are many constraints.
To produce arrays one must be able to reproducibly perform reactions at a particular site without affecting adjacent sites. The reaction should approximate stoichiometry in producing the desired product. Since many of the reactions are performed stepwise, any failure during the synthesis will result in the wrong product. One must be able to define the site at which the reaction occurs in a rapid and efficient manner. Each step in the process should provide for a reproducible result and not interfere with the next stage or the reaction at a different site.
Since the arrays should provide for a large number of different compounds, the process requires many steps. With oligonucleotides, each monomer addition involves a plurality of steps, so that the synthesis at each site will involve the number of steps for each addition multiplied by the number of monomers in the oligonucleotide. In order to be able to produce arrays of oligonucleotides efficiently, it is important to develop automated systems which provide for the accurate placement of reagents, efficient reaction, close packing of different compounds and the indexing of individual oligonucleotides with a particular site in the array. There is, therefore, a great interest in developing systems which will provide for rapid, accurate production of arrays of compounds, where the compounds are synthesized in situ, and the arrays have a high density and clear separation between sites. The apparatus must provide for assurance of the efficient synthesis and the ability to identify the product at a particular site.
In the past, preparation of these arrays was a slow, unreliable process. Moreover, where attempts have been made at automation, a lengthy, pre-synthesis preparation of masks was necessary, and undesirably large quantities of costly reagents were employed.